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Query: UMLS:C0009450 (infectious diseases)
 83,438 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the Australian livestock industries, susceptibility to infectious diseases is generally greater in young than in mature ruminants. The increased susceptibility is manifest as respiratory and intestinal infections (viral and bacterial) of calves, as well as fleece rot, flystrike and, especially, gastrointestinal parasitic infestations of young sheep. Lower resistance to infectious disease in young ruminants appears to be due largely to immunological hyporesponsiveness, and is not simply a consequence of their not having been exposed sufficiently to pathogens to develop active immunity. Young sheep have significantly lower proportions of CD4+ and CD8+ lymphocytes, but similar proportions of T19+ and B lymphocytes in blood, lymph and skin compared with mature sheep. Blood lymphocytes from young sheep produce less interferon-gamma in culture and young sheep invariably mount smaller antibody responses than do mature animals. Taken together, these findings begin to explain why young ruminants are more susceptible to infectious diseases in general, and to gastrointestinal parasites in particular, when compared to mature animals. Haematological markers of disease resistance, the prevalence of non-selected diseases and immune responses to vaccination were examined in the internal parasite-resistance flocks in Armidale NSW and the fleece rot/flystrike selection flocks at Trangie NSW. Any programme that seeks to improve resistance to parasitic or any other disease should have the capacity to make contemporary measurements of resistance to other diseases which are important in, or threaten, the production system.
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PMID:Some relationships between age, immune responsiveness and resistance to parasites in ruminants. 892 36

Onchocerciasis is a chronic infectious disease caused by the filarial nematode Onchocerca volvulus. A minor population of human gammadelta T cells expressing Vdelta1 chains is preferentially stimulated by O. volvulus ligands in vitro. Therefore, the nature of the parasite ligand and the effector functions of Vdelta1+ T cells stimulated by O. volvulus was investigated. A 5- to 30-kDa ligand from the adult parasite lysate that is sensitive to proteinase treatment was identified. Presentation for preferential stimulation of Vdelta1+ T cells required processing. After in vitro stimulation with O. volvulus in the presence of interleukin-2, Vdelta1+ T cells produced interferon-gamma but not interleukin-4 and exhibited NK cytolytic activities. It is concluded that somatic 5- to 30-kDa protein ligands from O. volvulus stimulate Vdelta1+ T cells and that Vdelta1+ T cells play a role in immunity to O. volvulus.
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PMID:Low-molecular-weight protein ligands from Onchocerca volvulus preferentially stimulate the human gammadelta T cell Vdelta1+ subset. 894 Feb 23

Toxoplasma gondii is an obligate intracellular parasitic protozoan that infects a variety of warm-blooded animals, including humans. Infection is usually asymptomatic in immunocompetent individuals but may be devastating in immunocompromised individuals such as those with acquired immunodeficiency syndrome (AIDS). Clinical manifestations of infection in immunocompromised patients include the development of encephalitis. It has been estimated that approximately 30% of patients with AIDS who are latently infected will eventually develop toxoplasmic encephalitis. The most common regimen used to treat toxoplasmic encephalitis is a combination of pyrimethamine 50 to 100 mg/d and sulfadiazine 4 to 8 g/d, with or without folinic acid 10 mg/d. This regimen, however, commonly leads to adverse effects or relapses. Other pharmacologic approaches include the use of clindamycin rather than sulfadiazine, the macrolide antibiotics, atovaquone, 5-fluorouracil, trimethoprim/sulfamethoxazole, minocycline or doxycycline, trimetrexate with folinic acid, dapsone, rifabutin, pentamidine, and diclazuril. None of these alternative regimens has been proven to be more effective than the standard pharmacologic therapy. An evolving approach is the use of immunotherapy, such as interleukin-2, -6, and -12; interferon-gamma; and alpha-tumor necrosis factor. Restoring a competent immune system may be the only cure for toxoplasmosis and other opportunistic infections.
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PMID:Treatment regimens for patients with toxoplasmic encephalitis. 900 22

Limited information is available about the pathogenesis of acquired immune deficiency syndrome (AIDS)-associated idiopathic interstitial pneumonitis, a common noninfectious complication of human immunodeficiency virus (HIV) infection. Infection of C57B1/6 mice with LP-BM5 retrovirus, a murine model of AIDS, leads to development of a diffuse interstitial pneumonitis that displays many features of human AIDS-associated interstitial pneumonitis. To further characterize the cellular and molecular features of this lung disease, the temporal development of cellular infiltration, cytokine expression, and virus replication were evaluated in lung tissue of virus-infected mice. Persistent expression of viral RNA was detectable in lungs as early as 1 wk after infection. Infiltration of the lungs by CD4+ and CD8+ T cells, by IgG+ and IgA+ B cells, and by macrophages was observed by 4 wk after infection and continued through 8 wk of infection. Histologically, cellular infiltration was most pronounced in peribronchial and perivascular regions, whereas inflammation of alveolar septae and alveolar spaces was minimal. In contrast to normals, T cells from infected lungs were immunodeficient in that they failed to proliferate in response to the mitogen concanavalin A (ConA). However, evaluation of cytokine mRNA expression by interstitial lung lymphoid cells indicated that cells from infected lungs were chronically activated, in that elevated expression of interferon-gamma (IFN-gamma) and interleukin-10 (IL-10) was observed throughout the course of infection. Similarly, expression by interstitial lung lymphoid cells of mRNA for the proinflammatory cytokine IL-1 and the fibrogenic cytokine transforming growth factor-beta (TGF-beta) was also increased following infection. These results indicate that retrovirus-induced immunodeficiency in mice is associated with infiltration and chronic activation of lymphoid cells in the lungs. Furthermore, simultaneous expression of IL-10, IFN-gamma, and TGF-beta suggests that cytokine-expressing cells in infected lungs may be unresponsive to inhibitory and antiinflammatory effects of IL-10 and/or TGF-beta, thus contributing to chronicity of inflammation in this disorder.
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PMID:Pulmonary lymphoid cell activation and cytokine expression in murine AIDS-associated interstitial pneumonitis. 903 22

The relation between gram-negative bacteremia, endotoxemia and cytokinemia in patients with hematological malignancies was studied. Serum endotoxin and cytokines (tumor necrosis factor-alpha, interleukin-1 receptor antagonist, interferon-gamma, interleukin-6 and interleukin-10) were determined in 24 patients with hematological malignancies. Patients were included at start of fever (n = 18) or during a temperature peak during continuous fever (n = 6; time = 0). Blood was drawn for cultures at time of inclusion. Additional samples were obtained and grouped in two time intervals (1-5 h and 6-12 h after inclusion). Endotoxin was detected in eight patients. Endotoxemia was more common among patients with bacteremia than among non-bacteremic patients (7/12 versus 1/12; p < 0.05). All studied cytokines showed a tendency to higher mean values at time 0 in patients with endotoxemia than in patients without endotoxemia. Significantly higher mean endotoxin values were seen at time 1-5 h in patients with gram-negative bacteremia (n = 6) than in patients without gram-negative bacteremia, and at time 0 in patients with chills (n = 6) compared to those without chills.
Infection
PMID:Endotoxemia in febrile patients with hematological malignancies. Relationship of type of bacteremia, clinical findings and serum cytokine pattern. 903 29

Distinct cytokine profiles are clearly associated with and relate to the severity of several types of infections. Cytokine networks are apparent with selected human infectious diseases, such as mycobacterial infections (leprosy, tuberculosis), the parasitic infection leishmaniasis, human immunodeficiency virus (HIV) infection, and gram-negative sepsis. Cytokine profiles are determined to some extent by two functional subsets of T lymphocytes, Th1 and Th2. The Th1 cytokines (interferon gamma, interleukin-2 [IL-2], IL-12) enhance cell-mediated immunity, inhibit humoral immunity, and result in protective effect for pathogens that are removed primarily through cell-mediated immunity (Mycobacterium tuberculosis, Mycobacterium leprae, Leishmania). The Th2 cytokines (IL-4, IL-5, IL-10, IL-13) enhance humoral immunity and inhibit cell-mediated immunity, and result in protective effect for pathogens removed primarily through humoral mechanisms. Progression of HIV infection is associated with a switch from a Th1 to a Th2 profile. For sepsis, uncontrolled activation of proinflammatory cytokines (IL-1, tumor necrosis factor-alpha, interferon-gamma) may be a fundamental defect that promotes the detrimental aspects of inflammation, whereas Th2 cytokines may be beneficial in controlling inflammation. Knowledge of basic cytokine immunopharmacology, networks, and relationships with infectious processes will aid clinicians in determining treatment approaches that are likely to be effective.
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PMID:Cytokine networks with infection: mycobacterial infections, leishmaniasis, human immunodeficiency virus infection, and sepsis. 908 11

Interleukin-12 (IL-12) is a heterodimeric cytokine that promotes cell-mediated immunity by facilitating type 1 helper T-lymphocyte responses, inducing the secretion of interferon-gamma from both T and natural killer cells, enhancing the lytic activity of natural killer cells, and augmenting specific cytolytic T-lymphocyte responses. In addition, IL-12 can increase the production of some subclasses of IgG antibodies. IL-12 has been shown to have potent therapeutic effects in a number of animal models of tumours and infectious diseases, including several viral infections. These results have led to the initiation of clinical trials to evaluate the therapeutic potential of IL-12 in human cancer patients and in patients infected with the human immunodeficiency virus. The biological activities of IL-12 suggest that it may also have clinical utility in the treatment of patients suffering from chronic hepatitis B or C virus infections. Because of the lack of suitable animal models for evaluating the efficacy of IL-12 in the treatment of infections with these viruses, only a clinical trial in patients with chronic viral hepatitis can address the potential role of IL-12 as an effective treatment for these disorders.
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PMID:Interleukin-12: potential clinical applications in the treatment of chronic viral hepatitis. 909 76

Infection with the human immunodeficiency virus (HIV) is accompanied by a decrease in CD4+ T cell numbers and the ultimate disruption of immunological functions. In sera of infected patients, elevated levels of interferon-gamma are detected, which is indicative of an activated TH1-type immune response. T-cell-derived interferon-gamma leads to the expression of various proinflammatory cytokines and enhanced macrophage capacity to secrete reactive oxygen intermediates. In addition, interferon-gamma is the major stimulator for the biosynthesis of neopterin and its reduced form, 7,8-dihydroneopterin. Neopterin is known as a sensitive immune activation marker in clinical laboratory diagnosis. Recent data implied a potential role of neopterin derivatives in oxygen free-radical-mediated processes, e.g. high concentrations of 7,8-dihydroneopterin were found to interfere with the oxidant-antioxidant balance, and may lead to apoptosis of human cells. In addition, 7,8-dihydroneopterin was found to be effective in the activation of redox-sensitive transcription factors and in the induction of HIV-1 gene expression. In this commentary, we describe our current view as to how neopterin derivatives, in concert with cytokines and reactive oxygen intermediates, may lead the way to the final destruction of the cellular immune system.
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PMID:Chronic immune stimulation, oxidative stress, and apoptosis in HIV infection. 911 96

Infection with Plasmodium berghei ANKA (PbA) causes fatal cerebral malaria (CM). While a pathogenic role for tumor necrosis factor (TNF) has been established, we asked whether a disruption of interferon-gamma (IFN-gamma) signaling would modulate CM. We demonstrate here that IFN-gammaR-deficient mice are completely protected from CM. PbA-induced release of TNF and up-regulation of endothelial intercellular adhesion molecule (ICAM)-1 expression, recruitment of mononuclear cells, and cerebral microvascular damage with vascular leakage occur only in wild-type mice. Protected mice die at a later time of severe anemia and overwhelming parasitemia. Resistance to CM in IFN-gammaR-deficient mice is associated with reduced serum TNF levels, reduced interleukin-12 expression in the brain and increased T-helper 2 cytokines. In conclusion, IFN-gamma is apparently required for PbA-induced endothelial ICAM-1 up-regulation and subsequent microvascular pathology, resulting in fatal CM. In the absence of IFN-gamma signaling, ICAM-1 and TNF up-regulation is reduced; hence, PbA infection fails to cause fatal CM.
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PMID:Interferon-gamma is essential for the development of cerebral malaria. 992 44

Mechanisms regulating the balance of T-helper 1 (Th1) and T-helper 2 (Th2) immune responses are of great interest as they may determine the outcome of allergic and infectious diseases. Recently, in mice, nitric oxide (NO), a powerful modulator of inflammation, has been reported to preferentially down-regulate Th1-mediated immune responses. In the present study, we investigated the effect of NO on the production of Th1- and Th2-associated cytokines by activated human T cells and human T-cell clones. Cytokine secretion was measured in the presence of the NO-donating agents 3-morpholinosydnonimine (SIN-1) and S-nitroso-N-acetylpenicillamine (SNAP). Both NO-donors markedly inhibited the release of interferon-gamma (IFN-gamma), interleukin-2 (IL-2), IL-5, IL-10 and IL-4 by anti-CD3 activated T cells. A preferential inhibition of Th1-associated cytokines was not observed. Neither was nitrite found in the supernatants of activated T cells, nor was specific mRNA for inducible and constitutive NO synthase detectable, indicating that T cells themselves did not contribute to the observed effect of the NO donors. Costimulation with anti-CD28 monoclonal antibodies (mAb) prevented SIN-1/SNAP-mediated down-regulation of cytokine production only in part. In contrast, when T cells were stimulated by phorbol-ester and ionomycin, they were refractory to SIN-1-induced inhibition of cytokine production. When SIN-1 was added after the onset of anti-CD3 stimulation, the inhibitory effect was found to be less pronounced, indicating that SIN-1 may interfere with early signal transduction events. The addition of superoxide dismutase (SOD) and catalase did not restore the effects of SIN-1, demonstrating that the inhibition of cytokines was due to NO and not to oxygen intermediates. Furthermore, 8-Br-cGMP-mediated increase of intracellular cGMP caused the same pattern of cytokine inhibition as observed with SIN-1 and SNAP. Using a single cell assay, these agents were shown to reduce the frequency of IFN-gamma-producing T cells, suggesting that not all T cells are susceptible to SIN-1/SNAP. However, cytokine production by purified T-cell subpopulations (CD4+, CD8+, CD45RA+, and CD45RO+) was equally impaired by NO donors. In conclusion, in contrast to the murine system, our results do not provide evidence that NO preferentially inhibits Th1-cytokine secretion of activated human T cells in vitro.
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PMID:Nitric oxide inhibits the secretion of T-helper 1- and T-helper 2-associated cytokines in activated human T cells. 913 48


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